Abstract: Hand, foot and mouth disease (HFMD) is a highly contagious viral disease caused by enteroviruses among infants and children. HFMD has recently emerged as a major public health concern and become an economic burden across the Asian-Pacific region, especially in China. For example, from 2008 to 2012, more than 9 million cases of HFMD were reported, resulting in around 2,700 reported deaths in China. Early, rapid and accurate identification of causative agents of HFMD is critical in the patient management and in the control of HFMD infection. Traditional virus confirmatory diagnosis methods are time-consuming and resource- intensive. Lateral flow immunochromatographic strip test is simple and instrument-free, but suffers from low sensitivity and specificity. PCR-based molecular diagnostics is both highly sensitive and specific for HFMD diagnosis. However, it requires expensive real-time PCR instruments, highly trained personnel, and labor- intensive operation, all of which are unsuitable for point-of-care (POC) use, in general, and unaffordable for low- and middle-income countries (LMICs). In collaboration with researchers in China, we propose to develop and validate a low cost, chemical-heating, mobile phone-based, molecular diagnostic device (dubbed ?smart cup?) for minimally-instrumented, on-site diagnosis of HFMD in rural China. We assemble a multidisciplinary research team and propose the following specific aims: i) develop and optimize the smart cup for HFMD molecular diagnosis, and ii) evaluate and validate the feasibility of the smart cup for clinical application at remote clinics in rural China. Our proposed smart cup is unique in: i) adapting a simple isothermal amplification strategy for rapid molecular diagnosis, ii) taking advantage of chemical exothermal reaction to produce the heating for isothermal amplification, eliminating the need for expensive electronic instruments, and iii) leveraging ubiquitous mobile phone technology to record, analyze and report the test results without the need for specialized optical detectors. With our international, interdisciplinary team, this project will promote technology transfer between UPenn and China, and strengthen the link with Chinese researchers and health care workers at remote clinics. The pilot-test data obtained in this project will be the basis for future larger- scale research on implementation and scale-up of our smart cup in rural areas. The innovation's benefits will not be limited to HFMD diagnosis; if successful, it will be easily adaptable to other pathogens (i.e., HPV, HIV).